The monoterpenes ⍺-pinene and limonene augment or mitigate THC-induced impairments in sustained attention in rats.

RATIONALE: α-pinene and limonene are two monoterpenes found in cannabis and cannabis products containing Δ-9-tetrahydrocannabinol (THC). These terpenes are often purported to alter the effects of THC, but empirical data are lacking. OBJECTIVES: The current study sought to determine whether orally administered α-pinene and limonene in combination with THC, would mitigate or augment the adverse effects of THC on performance of a cognitive task of sustained attention in rodents. METHODS: Male and female Sprague-Dawley rats (n = 24, 50% female) were trained in the rodent psychomotor vigilance task (rPVT). Rats received single or combined doses of THC (3 and 10 mg/kg) and one terpene (10-100 mg/kg; limonene or α-pinene) or vehicle (sesame oil) via oral gavage 60-min prior to rPVT test sessions. Data were analyzed with linear mixed models with sex, THC dose, and terpene dose as factors, accepting p < 0.05 as significant. RESULTS: THC dose-dependently reduced accuracy and increased lapses in the rPVT. When administered alone, α-pinene tended to reduce accuracy and increase lapses at the highest dose (100 mg/kg); limonene alone had no effect on rPVT performance at any doses tested. α-pinene (100 mg/kg) exacerbated performance impairments when administered in combination with a moderate dose of THC (3 mg/kg) but mitigated some effects of a high dose THC (10 mg/kg) on rPVT performance (at α-pinene doses 10-30 mg/kg). Limonene (10-100 mg/kg) mitigated performance impairments from 3 mg/kg THC, but not 10 mg/kg THC. CONCLUSIONS: These data lend support to the idea that terpenes found in cannabis can modulate the cognitive effects of the psychoactive constituent THC.